Within the past year substances that are mutagenic on the Salmonella/mammalian microsome test (Ames test) have been found in the feces of some North Americans. Since almost all carcinogens are mutagens, the presence of mutagens in the colon could be responsible for the high incidence of large bowel cancer in affluent populations. This belief is supported by our finding that the excretion of fecal mutagens occurred in a significantly larger proportion of a population at high risk for colon cancer (South African urban whites and North Americans) than in a population at very low risk (rural black South Africans). We propose to continue our population studies to determine whether excretion of mutagens is correlated with risk of large bowel cancer, but first we need to determine the best way to extract and separate the mutagens. This will allow us to determine whether excretion of all mutagens is correlated with level of risk to colon cancer or whether only certain ones are involved. If the presence of certain mutagens in feces is associated with a high risk of colon cancer, we will work on developing a rapid screening test that will be needed to identify such individuals. We have found that the mutagenicity of fecal extracts can be eliminated by incubating the mutagens with feces from persons who do not excrete such mutagens. This suggests that the anaerobic fecal flora of most people may inactivate the mutagens. We propose to determine whether this is true, and if so to determine which organisms are responsible. We will also study whether anaerobes may produce these compounds from dietary components or endogenous compounds.